The Type III secretion system of Gram-negative bacteria: a potential therapeutic target?

Several pathogenic Gram-negative bacteria, including Salmonella, Shigella, Yersinia, Pseudomonas aeruginosa and enteropathogenic Escherichia coli harbour a complex attack system called 'Type III secretion' which is, in every case, an essential virulence determinant. This system, activated by contact with an eukaryotic cell membrane, allows bacteria to inject bacterial proteins across the two bacterial membranes and the eukaryotic cell membrane, to reach the cell's cytosol and destroy or subvert the host cell. The Type III virulence mechanism consists of a secretion apparatus, made up of about 25 proteins, and a set of effector proteins released by this apparatus. The mechanism of protein secretion is highly conserved among the different bacteria, although they cause a variety of diseases with different symptoms and severities, from fatal septicaemia to mild diarrhoea or from fulgurant diarrhoea to chronic infection of the lung. This review focuses on the proteins that make up the secretion machinery and examine if it could be a potential target for novel antimicrobials.